transfusion. trali and taco ob - medigraphic · volumen 34, suplemento 1, abril-junio 2011 rivers...

Revista Mexicana de AnestesiologíaS322

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Transfusion.TRALI and TACO OB

Jose M. Rivers. MD*

*Associate Professor. Baylor College of Medicine. Houston, Texas

C

CONFERENCIAS MAGISTRALESVol. 34. Supl. 1 Abril-Junio 2011

pp S322-S333

CAUSES OF MATERNAL DEATH

Severe bleeding (Haemorrhage) 25% Infection 15% Eclampsia 12% Obstructed labour 7% Unsafe abortion 13% Other direct causes 8% Indirect causes 20%

Source: The World Health Report 2005. Make every mother and child count Geneva, World Health Organization, 2005

TRANSFUSION FACTS

• 80 million units donated worldwide yearly1

• 20 million units transfused each year in the United States2

• A blood transfusion is the most intimate possible contact with a stranger

Preoperative period 4.23% Intraoperative to 48 hours after surgery 36.62% Period 48 hours after surgery until discharge 59.15%

1. World Health Organization. Available atwww.who.int/bloodsafety/en/blood_Transfusion_Safety.pdf2. Goodnough LT, et al. N Engl J Med. 1999;340:438-447.

TRANSFUSION REQUIREMENTS IN CRITICAL CARE (TRICC)

Prospective, randomized trial that supports causal link be-tween blood transfusion and adverse outcomes among criti-cally ill patients

Hébert PC, et al. N Engl J Med. 1999;340:409-417.

BLOOD TRANSFUSION COMPLICATIONS

80

Com

plic

atio

ns

70

60

50

40

30

20

10

01 2 3 4

Relationship between the number of units of blood and postoperative complications. Columns indicate the percentage of complications related to the number of units of blood transfer


http://www.medigraphic.com/espanol/e1-indic.htm

Volumen 34, Suplemento 1, abril-junio 2011

Rivers JM. Transfusion. TRALI and TACO OB

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60

50Units of blood

40

30

20

10

01 32 4 5

Non

-sur

vivo

rs

Relationship between the number of units of blood and mortality columns indicate the percentage of non-survivors in relation to the number of units of blood transfused


• Infectious disease• Complications resulting from misidentification or clerical error• Transfusion-related acute lung injury• Bacterial contamination• Immunomodulation• Unknown mechanism

35Percentage of patients exhibiting complications

Myoca

rdial

infar

ction

Left v

entric

ular

failur

e

Respir

atory

failur

e

Postop

erati

ve

death

Infec

tion

(minc

e or m

ajor)

Geber

al se

psis

Renal

failur

e

Pneum

onia

25

20

15

10

5

0

Patient NOT receiving blood transfusion Patients receiving transfusion

INFECTIOUS DISEASES

• Human immunodeficiency virus risk: 1:2.3 million1

• Hepatitis C risk: 1:1.8 million1

• Hepatitis B: 78,000 new infections annually, United States2

• Risk of transmission through transfusion of 1 unit of blood, 1:58,000-1:149,0003

• Other viral diseases4,5

• West Nile: 2539-9862 cases in United States between 2002 and 20064

• Cytomegalovirus: 40%-100% of US population shows prior exposure by serology5

• Malaria: 300-500 million cases worldwide6

• Chagas disease: »1 million new cases annually*6

• Prions6

*In humans, confined to South and Central America and Mexico.1. Busch MP, et al. Transfusion. 2005;45:254-264; 2. Centers for Disease Control and Prevention. Available at: www.cdc.gov/vac-cine/pubs/pinkbook/downloads/hepb.pdf. Accessed March 3,2008; 3. Goodnough LT, et al. Lancet. 2003;361:161-169; 4. Centers for Disease Control and Prevention. Available at: www.cdc.gov/ncidod/dvbid/westnile/surv&controlCaseCount. Accessed March 3, 2008; 5. Taylor GH. Am Fam Physician. 2003;67:519-524,526; 6. Snyder EL, et al. Hematology. 2001;433-442.

NONINFECTIOUS SERIOUS HAZARDSOF TRANSFUSION (NISHOTS)A

Immune mediated Hemolytic transfusion reaction Febrile nonhemolytic transfusion reactions Allergic/urticarial/anaphylactic transfusion reaction Transfusion-related acute lung injury (TRALI) Posttransfusion purpura (PTP) Transfusion-associated graft versus host disease (TA-

GVHD) Microchimerism Transfusion-related immunomodulation (TRIM) Alloimmunication

Nonimmune mediated Septic transfusion reactions Nonimmune hemolysis Mistransfusion Transfusion-associated circulatory overload (TACO) Metabolic derangements Coagulopathiac complications from massive transfusion Complications from red cell storage lesions Over/Undertransfusion Iron overload

Revista Mexicana de Anestesiología


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PATIENT IDENTIFICATION IS CRITICAL

• Identify at time of phlebotomy• Ask patient his/her name• Verify identity with wrist band• Label tube at bedside

• Identify at time of transfusion• Two people must identify patient and verify match to

label on blood product• If there are ANY discrepancies when blood sample and

paperwork arrive at blood bank• It is 40 times more likely that the wrong patient’s blood

is in the tube than if all identifying information is com-plete and matches

WHAT IS TRALI AND TACO

• TRALI• Transfusion-related acute lung injury

• TACO • Transfusion associated circulatory overload

• Pulmonary complications of blood transfusions

TRANSFUSION-RELATED FATALITIES BYCOMPLICATIONS, FY 2005 THROUGH FY 2008

SUMMARY OF TRANSFUSION ERRORS 2006-2009

Medication administered with blood

Patient refused but transfused

Transfused but not indicated

Contra-indicated medication

Computer related error

Technical error

Wrong ABO FFP transfused

No crossmatch but transfused

Mislabeled crossmatch sample

Units transfused/not ordered

Misidentified on issue/transfusion

FFP = fresh frozen plasma.Data on file, US Department of Veterans Affairs.

2520151050

40

30

Complication

TRALI

29FY 05

FY 06

FY 07

FY 08

16 8 6 1 0 2

35 9 7 3 8 1 0

34 2 6 3 5 2 0

16 7 7 10 3 3 0

HTR(non-ABO)

HTR(ABO) OtherAnaphylaxisTACO

Microbial infection

20

10

0

Axi

s tit

le



S325


Este documento es elaborado por Medigraphic



S326




S327


CASE PRESENTATION

• 22 year-old, ASA 1 G3P2 at 40 weeks with vaginal bleeding.

• One prior classical cesarean delivery• She was to undergo urgent repeat C/S• CSE was performed without complications with hyperbaric

bupivacaine 0.75% (10 mg), fentanyl 10 mg and 0.2 mg preservative-free morphine

• After delivery severe uterine atony.• Pitocin 30 units by continuous infusion • Methylergonovine 0.2 mg IM• Carboprost X 2 IM and intramyometrial• Hemodinamically stable for first 45 minutes • Hypotension and significant oozing in surgical field.• Supracervical hysterectomy • EBL: 4 L. LR: 6 L. Hetastarch: 500 cc• PRBCs 7 units. FFP 6 units Platelets: 10 units• During skin closure: Dyspnea, tachypnea and O2 satura-

tion 85%• Mental changes• RSI, intubation and mechanical ventilation• Copious amount of frothy secretions• Transferred to SICU• PA catheter placed: PCWP: 16 mmHG, PA pressure 46/30,

CO 6.0 L/min• Over next 2 hours worsening hypotension and hypoxemia• Norepinephrine infusion and vasopressin

Pre

ssur

e

70

60

50

40

30

20

10

10 12Time of day

PEEP W PIP CO PaO2

14 1611 13 15 170

• Increasing ventilatory support• Inhaled nitric oxide.• Nine hours postoperatively. Veno-Arterial ECMO.• Soon after ECMO, patient hemodynamically stable. Me-

chanical ventilation weaned over next seven days• Discharged home on postoperative day 33

DIFFERENTIAL DIAGNOSIS OF TRANSFUSION ASSOCIATED-RESPIRATORY DISTRESS

• TRALI• Circulatory Overload (TACO)• Allergic/Anaphylactic transfusion reaction• Bacterial contamination• Acute hemolytic reaction• Not transfusion related

TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI)

• First cases described in 1950’s• AKA

• Pulmonary leukoaglutinin reaction• Allergic pulmonary edema• Pulmonary hypersensitivity reaction• Non-cardiogenic pulmonary edema

• TRALI coined by Popovsky and Moore

TRALI

• Defined as ALI/ARDS developing during or within 6 hours of a blood product transfusion

• Immunologic reaction leading directly to ALI• Must exclude volume overload or cardiogenic pulmonary

edema• Must exclude other causes of ALI/ARDS



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2004 CONSENSUS PANEL CRITERIA FOR TRALI

• Acute lung injury• Acute onset• Hypoxemia

• SPO2 < 90% on room air or other clinical evidence of hypoxemia

• PaO2/FiO2 ratio < 300 mmHg• Bilateral infiltrates on frontal CXR• No evidence of left atrial hypertension (e.g. circula-

tory overload)• No preexisting ALI before transfusion• During or within 6 hours of transfusion• No temporal relationship to an alternative risk factor

for ALI

Transfusion 2004;44:1774-1789

DIFFERENTIAL DIAGNOSIS OF TRANSFUSION ASSOCIATED-RESPIRATORY DISTRESS

TRALI-EPIDEMIOLOGY

• Incidence:• 1-5,000 blood products transfused• 1 in 400 patients transfused• Under-reported and under-recognized • Fatal in 5-10% cases

PATHOGENESIS

• TRALI has been associated with all plasma-containing products• Whole blood, PRBCs, FFP, platelets are the most com-

monly identified causes.• Allogenic stem cells, cryoprecipitate, intravenous im-

munoglobulin and granulocytes• High plasma volume products (FFP and platelets) are

the most implicated products• Even small amounts of plasma can trigger the reaction.



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THREE HYPOTHESIS FOR TRALI

• Antibodies to human leukocyte antigens or antigranulocyte antibodies in donor’s plasma (or, less commonly, recipi-ent’s plasma)

• Biologically active substances in transfused blood• «2-hit» hypothesis

• Recipient granulocytes are primed in vivo, then trans-fused antibodies «activate» granulocytes

Toy R, et al. Best Prac Res Clin Anaesthesiol. 2007;21:183-193

PATHOGENESIS

Effect of blood product storage time

• Corpuscular and supernatant effects• RBCs become more rigid• Cytokines accumulate with increased storage time; pro-

inflammatory lipids accumulate• Less of a problem with universal leukoreduction

THREE HYPOTHESIS FOR TRALI

• Antibodies to human leukocyte antigens or antigranulocyte antibodies in donor’s plasma (or, less commonly, recipi-ent’s plasma)

• Biologically active substances in transfused blood• «2-hit» hypothesis

• Recipient granulocytes are primed in vivo, then trans-fused antibodies «activate» granulocytes

Toy R, et al. Best Prac Res Clin Anaesthesiol. 2007;21:183-193

TRALI: 2-HIT HYPOTHESIS

Predisposing condition• Recent surgery• Trauma• Active infection or inflammation• Cytokine administration• Massive transfusion

Blood products (any)• Anti-granulocyte antibodies• Anti-HLA antibodies• Biologically active lipids

REPORTS OF TRALI BY IMPLICATED BLOOD PRODUCTS, FY2005 THROUGH FY 2008

Num

ber

30

20

FFP

13 5 3 4 4

22 5 1 2 5

12 12 0 1 9

4 5 0 5 2

Plasma*

Blood products

Platelets pheresis

Multiple productsrbc

10

0

a

PMN Blood flow

EC

b

c



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TRALI: PATHOGENESIS

Pulmonary edema

Increased microvascular permeability

Leukocyte antibodies 2-«event» model

CLINICAL FEATURES

• Onset• Sudden• Classically, 30-60 min after initiation of transfusion,

with a range of 0-6 hours• Signs and symptoms

• Fever, hypotension, tachycardia, and tachypnea• Hypoxemia often requiring mechanical ventilation• CXR: bilateral alveolar infiltrates consistent with ALI/

ARDS

TRALI: WHO IS AT RISK?

• Recent surgery• Induction chemotherapy• Cardiopulmonary bypass• Massive transfusion• TTP• No difference in gender, age

Bux et al. Brit J Haem 2007;136:788-799

TREATMENT

• Stop the transfusion!• Rule out other causes of pulmonary edema, especially

volume overload or cardiac dysfunction• Possibility of co-existing permeability and hydrostatic

edema• ARDSnet ventilatory strategy• Diuretics may be harmful• No role for corticosteroids• Remember that with supportive care, most patients will

recover quickly



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TRALI OUTCOMES

Condition Cases (n) Cases (%)

Oxygen support 36 100Mechanical ventilation 26 72Pulmonary infiltrates 36 100Rapid resolution (< 96 h) 29 81Slow resolution (> 7 days) 6 17Mortality 2 6Long-term sequelae 0

TRALI PREVENTION

• Mutiparous donors• 20-25% possess HLA antibodies• Implicated in look-back studies (Kopko, JAMA)• 1/3 of female apheresis donors in one study

• UK SHOT initiative• Male only FFP• Pooled platelets suspended in male plasma

• AABB has recommended that high plasma volume blood products (FFP), platelets be obtained from males or females with no history of pregnancy• Female donors>>>PRBCs and other plasma-poor prod-

ucts• FFP policy has been implemented• Platelet deferral ongoing

CONCLUSION

• TRALI is the #1 cause of transfusion-associated mortality• TRALI is a clinical diagnosis that can be made at the

bedside• Blood within 6 hours + ALI/ARDS = TRALI• Role of HLA and neutrophil antibodies and prevention in

TRALI

TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD (TACO)

Definition/mechanism

• Pulmonary edema due to transfusion• Too much blood + non-sanguineous fluid• Transfused too rapidly• Cardiogenic• Role of cytokines?

TACO: CLINICAL PROFILE

Risk factors Very young/oldOnset < 2 hours of transfusionSymptoms Respiratory distress, cyanosis, headache, dry coughSigns BP; systolic > diastolic; HR; CVP: wedge pressureLaboratory B-natriuretic peptide

TACO: DIAGNOSIS ROLE OF B-NATRIURETIC PEPTIDE

• Neurohormone released from ventricular myocardium in response to ventricular volume & pressure distension

• First introduced to diagnose CHF• Zhou et al: Post/pre-transfusion ratio of 1.5, sensitivity of

81% & specificity of 89% to diagnose TACO• Tobian et al: Comparable finding• Reference

• Zhou et al. Transfusion 2005;45:1056-63• Tobian et al. Transfusion 2007;47:7A

3000

2500

2000

1500

1000

BN

P le

vel (

pg/m

L)

500

Pretrans-fusion control

Postrans-fusion control

Pretrans-fusion TACO

Postrans-fusion TACO

0

TACO: MANAGEMENT

• Stop transfusion• Provide supplementary oxygen• Reduce plasma volume with diuretics• Place patient in sitting position• If symptoms continue:

• Repeat the use of diuretics• Phlebotomize in 250 mL increments• Laboratory testing:• First tier testing



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TACO: SUMMARY

• TACO is an important clinical diagnosis• Significant morbidity• Increased recognition of mortality

• It is a frequent complication of transfusion• It is under-recognized and under-diagnosed• Confused with TRALI

TRALI VS TACO

Comparison of the features of transfusion related acute lung injury and transfusion associated circulatory overload

Feature TRALI TACOBody temperature Fever can be present UnchangedBlood pressure Hypotension HypertensionRespiratory symptoms Acute dyspnea Acute dyspneaNeck veins Unchanged Can be distendedAuscultation Rales Rales, S3 may be presentChest radiograph Diffuse, bilateral infiltrates Diffuse, bilateral infiltratesPA occlusion pressure 18 mmHg or less Greater than 18 mmHgPulmonary edema fluid Exudate TransudateFluid balance Positive, even, negative PositiveResponse to diuretic Minimal SignificantWhite count Transient leukopenia UnchangedBNP < 200 pg/mL >1,200 pg/mLLeukocyte antibodies Donor leukocyte antibodies present, Donor leukocyte antibodies may or may not crossmatch incompatibility between be present, positive results can suggest TRALI donor and recipient even with true TACO cases

Transfusion-related fatalities by complications, FY 2005 through FY 2008

transfusion. trali and taco ob - medigraphic · volumen 34, suplemento 1, abril-junio 2011 rivers...

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